Experimental animals (sheep) will be used for basic research into the physiology of endogenous morphine-like peptides (opioids). Previous research has estalished that these endogenous opioids are present in blood plasma and cerebrospinal fluid (CSF). The present project will determine the extent to which the pituitary gland is the source for beta-endorphin (beta-E), one of these blood-borne and CSF-borne opioids. It will also investigate factors such as stress and exogenous morphine which may influence secretion of opioids into blood and CSF. In addition, the efficiency of uptake of pituitary-derived beta-E by the opioid receptors in the brain will also be determined. Radioimmunoassay procedures will be developed for validly quantifying beta-E in plasma and CSF from sheep. Methods will also be developed for sampling simultaneously in unstressed animals hypothalamic venous effluent plasma and arterial plasma as well as 3rd ventricle CSF. Surgical procedures of hypophysectomy and transection of the pituitary stalk will be performed in order to quantify the amount of beta-E secreted into bloood and CSF by the pituitary gland as well as the retrograde delivery of pituitary-derived opioids to the hypothalamus in locally high concentrations. The ability of the narcotic antagonist naloxone to block the opioid receptors will be used to quantify the efficiency of opioid uptake by receptors in vivo. A number of situations will be explored to determine if they influence the in vivo release of pituitary opioids using beta-E as the endogenous opioid most readily quantified. These situations include (1) initiation of morphine in narcotically naive subjects, (2) withdrawal of morphine administration in addicted subjects, (3) acute stress, (4) endotoxin-induced vascular shock, and (5) induced alterations of cerebral and pituitary blood flow.